Association between p16/Ki-67 dual stain cytology results prior to and 6months after LLETZ treatment for CIN and the follow-up regimen three years after treatment: a retrospective cohort study.

Abstract

Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment. Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-riskHPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according tothe Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visitsbecause of persistent hrHPV infection orabsence of cytological regression). The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment. This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.